| Annotated protein: | Kinesin-like protein KIF21B (Kinesin-like protein KIF6). Gene symbol: KIF21B. Taxonomy: Mus musculus (Mouse). Uniprot ID: Q9QXL1 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ KIF21B |
| Ontology domain: | Biological Process |
| SynGO term: | retrograde dendritic transport (GO:0098934) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Morikawa M, et al. "The Molecular Motor KIF21B Mediates Synaptic Plasticity and Fear Extinction by Terminating Rac1 Activation" Cell Rep. 2018 Jun 26;23(13):3864-3877 PMID:29949770 |
| Figure(s): | Figures 1-7 |
| Annotation description: | Figure 2: KIF21B is essential for AMPAR endocytosis. Knockout mice have a deficit in hippocampal LTD (ephys), fail to internalize GluR2 (GRIA2) upon NMDA stimulus and have impaired structural plasticity (unchanged spine density after stimulus). Figure 3: Y2H and reverse-IP assays showed KIF21B conditionally binds to ELMO1. Figure 4: KIF21B regulates the exit of ELMO1 from the dendritic spine. Time-lapse fluorescence micrographs of ELMO1-TagRFP-transfected dissociated hippocampal neurons revealed impaired ELMO1 dendritic spine-to-shaft translocation in KIF21B knockout mice. Figure S5, related to Figure 4 and 5: Accumulated KIF21B and ELMO1 co-localize with early and late endosomes. Figure 5, 6: Homotypic fusion of endosomes induces KIF21B and ELMO1 accumulation and KIF21B-dependent ELMO1 accumulation universally occurred upon NMDAR-mediated LTD. Authors conclude that "KIF21B sequesters ELMO1 Rac1GEF from dendritic spines to shaft endosomes". "We identified a Rac1 activity cycle in wild-type hippocampal neurons (Figures 7A and 7B) that is terminated through an atypical scaffolding activity of KIF21B kinesin for ELMO1 that is essential in driving the spine-to-shaft translocation of ELMO1 (Figures 4C-4E). This cycle was considered fundamental to NMDAR-dependent LTD expression because KIF21B/ELMO1 accumulation was consistently induced by the chemical, electrical, or behavioral stimuli that cause NMDAR-mediated LTD and fear extinction (Figure 6), and pharmacological recovery of this Rac1 cycle by CPYPP could significantly restore the LTD-associated cellular and behavioral phenotypes in Kif21b -/- mice (Figures 7G-7I and 7L-7S)." |
| Evidence tracking, Biological System: | Intact tissue Cultured neurons |
| Evidence tracking, Protein Targeting: | Genetic transformation (eg; knockout, knockin, mutations) Over-expression Antibody (detection) |
| Evidence tracking, Experiment Assay: | Electron Microscopy Confocal Y2H IP + WB/MSMS |
| Annotator(s): | Frank Koopmans (ORCID:0000-0002-4973-5732) Guus Smit (ORCID:0000-0002-2286-1587) Matthijs Verhage (ORCID:0000-0002-2514-0216) |
| Lab: | Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands |
| SynGO annotation ID: | 5201 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |